PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS – MARKERS IN CARCINOGENESIS AND CHEMOPREVENTIVE TREATMENT
Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors. Three major types have been identified: PPARï¡ï€¬ï€ PPARï¢ (PPAR ï¤), PPAR ï§. They are involved in the regulation of various types of tumors, inflammation, angiogenesis, diabetes and infertility. On activation by endogenous secreted prostaglandins and fatty acid, they initiate transcription of an array of genes that are involved in ener gy homeostasis. Activation of nuclear hormone receptors have been also identified as an approach to regu late differentiation, cell growth and inhibit proliferation of cancer lines. Studies of the differentiative effects of PPAR activators on several cancer cell lines led to hypothesis that dysfunction of PPARs contributes to tumorigenesis. Anti -proliferative, pro-differentiation effects of exogenous PPAR agonists (thiazolidinediones - TZDs) suggest that these compounds might be useful in slowing the proliferation of undifferentiated tumor cells. With the recent discovery that anti -diabetic class of drags thiazolidinediones act through activation of PPARï§, interest in this transcription factor has increased as it can now be pharmacologically activated in order to obtain tumor suppression. Furthermore, recent studies also show that PPARï§ï€ ligands are potent inhibitors of neoangiogenesis, a process essential for solid-tumor growth and metastasis. TZDs inhibit proliferation of human breast, prostate and colon cancers, both in vitro and in tumors derived from these cells implanted into rodents. This represents an exciting n ovel therapeutic application of TZDs. Although PPARï§ agonist may not by themselves be capable to induce clinical tumor regression, their combination with chemotherapy drags or other targeted therapies is worth pursuing in the treatment of endometrial carcinoma